HIV-1 gp41 by a common immunological epitope induces increased levels of antibodies against human interferon-β in HIV-1 positive individuals

Based on our finding that a similar epitope exists between human IFN-β (aa128–134) and HIV-1 gp41 (aa586–595), we examined 20 sera from healthy and 20 from HIV-1 infected individuals for IFN-β antibody levels by ELISA. The levels of anti-IFN-β antibody in sera from HIV-infected individuals were increased by about 160% in comparison with HIV-negative. We affinity-purified anti-gp41 antibodies from sera of HIV-1-infected individuals using rsgp41-sepharose column. One of three antibodies could recognize human IFN-β in comparison with antibodies from serum of a healthy individual. A mouse antiserum to human IFN-β recognized rsgp41 (recombinant soluble gp41, Env amino acid 539–684), while the normal mouse serum (pre-immune serum) did not bind to rspg41. These results indicate that a common immunological epitope exists between human IFN-β and HIV-1 gp41. The sequence-similarity suggests that this common immunological epitope may be located in the region aa128–134 of human IFN-β and the immunosuppressive domain (aa583–599) of HIV-1 gp41. The increased levels of antibodies against interferon-β in HIV-1 positive individuals may be explained by a common immunological epitope on human IFN-β and HIV-1 gp41.     

Immunological properties of two related fragments from human and equine growth hormones

The immunological properties of a synthetic human growth hormone fragment comprising the amino acids 73 through 128 and of the homologous natural horse growth fragment formed by amino acids 73 through 123, have been comparatively studied. Antisera obtained in rabbits inoculated with the native human hormone or with the fragments, were used. By hemagglutination experiments both fragments have the same reactivity toward the anti-human growth hormone serum, but complement fixation curves detect the existence of at least two populations of antibodies presumably originated against the sequence 73-128 of human growth hormone. Of these, only one of the corresponding antigenic areas is present in the homologous region of equine growth hormone. The known cross-reactivity detected between both hormones is thus partially explained.     

A novel method for the production of antibodies against ACTH: their characterization and use in epitope mapping

Our earlier attempts at immunization with human adrenocorticotropin hormone (ACTH) were unsuccessful and we therefore developed a new strategy including the chemical modification of the hormone by succinic anhydride in order to increase its immunogenicity. This process allowed us to obtain antisera with titers of up to 1/1000 and yielded 39 anti-succinylated ACTH (sACTH)-secreting hybridomas. Subsequently, the epitopes of sACTH were mapped by testing monoclonal antibodies two by two for simultaneous binding to sACTH and for their capacity to recognize its succinylated fragments 1–13, 1–17 and 1–24. The results, obtained with the use of radioactive tracers, were confirmed by and complemented with experiments conducted with biosensor technology. Seven groups of antibodies were defined on the basis of their pattern of reactivity and it was shown that four monoclonal antibodies could bind simultaneously to sACTH. Their dissociation constants (K_d) for sACTH were calculated and ranged from 10⁻⁸ M to 10⁻¹¹ M. In order to obtain a fast and sensitive immunoassay for the hormone, we developed a protocol for the chemical modification of ACTH in serum and the most efficient monoclonal antibodies were selected on the basis of the epitope map and of their dissociation constants.     

Analysis of antibody response to the measles virus using synthetic peptides of the fusion protein Evidence of non-random pairing of T and B cell epitopes

The measles virus induces a life-long immune response associated with antibodies specific for the fusion protein. To map the linear immunodominant recognition sites of the fusion (F) protein of the measles virus, we have reacted a complete set of 108 overlapping pentadecapeptides with purified IgG obtained from donor sera with elevated anti-measles titers. The antibodies recognized about 20% of the peptides and generated a characteristic binding pattern, defining about 6 or 7 distinctive regions (31–75; 111–145; 151–165; 191–215; 271–320; 421–440; 481–530) which include the major hydrophobic segment (111–145) of the intersubunit region and the C-terminal Cys-cluster region. The binding sites were located in close proximity of the few experimentally defined T cell epitopes. This pairing of T and B cell epitopes was corroborated by computer-assisted T cell prediction. The significance of a non-random association of T and B cell epitopes for processing and presentation is discussed. It is speculated that in long-term immunity against measles (F protein), B cells of the same sIg specificity play an important role both as antigen presenting cells and as antibody producing cells. In contrast to human sera from late convalescent donors, mouse and rabbit MV antisera with high neutralizing titers as well as neutralizing MV-F specific monoclonal antibodies did not react with the peptides.     

The recognition by monoclonal antibodies of various portions of a major antigenic site of human growth hormone

The reactivities of five mouse monoclonal antibodies against human growth hormone (hGH) were defined by either a competitive radioimmunoassay with insolubilized antibodies or by an agglutination-inhibition method with hGH-coated polystyrene particles. The five antibodies reacted significantly but to various degrees with human placental lactogen and at least three antibodies reacted with human prolactin and three synthetic peptides extending from residues 19 to 128, 73 to 128 and 98 and 128 of hGH. Four tested monoclonal antibodies failed to react with bovine growth hormone and with hGH oxidized by performic acid. The antibodies were further distinguished by their different reactions with hGH modified by reduction and alkylation or by adsorption on a polystyrene surface. The unique specificity of each antibody was confirmed for most of them by an agglutination method in which the agglutinating activity of hGH was tested on latex particles coated with various paired combinations of the monoclonal antibodies. The lack of agglutination with certain combinations suggested that the specificities of such a pair of antibodies overlapped each other. These results suggest that the sequences corresponding to the synthetic peptides participate in the structure of a major antigenic site of which various portions are recognized by the monoclonal antibodies.     

Growth hormone response to growth hormone-releasing peptide-2 in growth hormone-deficient little mice

OBJECTIVE:

To investigate a possible direct, growth hormone-releasing, hormone-independent action of a growth hormone secretagogue, GHRP-2, in pituitary somatotroph cells in the presence of inactive growth hormone-releasing hormone receptors.

MATERIALS AND METHODS:

The responses of serum growth hormone to acutely injected growth hormone-releasing P-2 in lit/lit mice, which represent a model of GH deficiency arising from mutated growth hormone-releasing hormone-receptors, were compared to those observed in the heterozygous (lit/+) littermates and wild-type (+/+) C57BL/6J mice.

RESULTS:

After the administration of 10 mcg of growth hormone-releasing P-2 to lit/lit mice, a growth hormone release of 9.3±1.5 ng/ml was observed compared with 1.04±1.15 ng/ml in controls (p<0.001). In comparison, an intermediate growth hormone release of 34.5±9.7 ng/ml and a higher growth hormone release of 163±46 ng/ml were induced in the lit/+ mice and wild-type mice, respectively. Thus, GHRP-2 stimulated growth hormone in the lit/lit mice, and the release of growth hormone in vivo may be only partially dependent on growth hormone-releasing hormone. Additionally, the plasma leptin and ghrelin levels were evaluated in the lit/lit mice under basal and stimulated conditions.

CONCLUSIONS:

Here, we have demonstrated that lit/lit mice, which harbor a germline mutation in the Growth hormone-releasing hormone gene, maintain a limited but statistically significant growth hormone elevation after exogenous stimulation with GHRP-2. The present data probably reflect a direct, growth hormone-independent effect on Growth hormone S (ghrelin) stimulation in the remaining pituitary somatotrophs of little mice that is mediated by growth hormone S-R 1a.     

The effects of hormone substitution in depot form on the uterus in a group of 50 perimenopausal women — a vaginosonographic study

The aim of our study was to examine the effects of hormone replacement on the size of the uterus and the development or increase of myomatas. Fifty perimenopausal women were included in the study (53.8 ± 5.0 years). Patients received a substitution therapy composed of a combination of 4 mg estradiolvalerate and 200 mg prasteronenantate (Gynodian^® Depot cartridges) given as a muscular injection in 6–10 week intervals (mean 7 weeks ± 4 days). Prior to the onset of therapy with Gynodian^® and after a period of 12 months (± 13 days) vaginosonography was performed. Measurements taken were length, thickness, height of endometrium, size of ovaries and of myomas. Data obtained were correlated with baseline findings. Within 1 year, significant increases in uterus length from 73.4 mm to 88.2 mm, in uterus thickness from 33.9 mm to 43.5 mm and in endometrium height from 4.1 mm to 6.7 mm were observed (median values). There was an increase in both the number (from 2.2 to 3.5) and the size of the myomatas (29.4–35.0 nm diameter). A statistical analysis conducted by means of the Wilcoxon matched pairs signed-rank sum test showed P < 0.001. No significant change occurred in the size of the ovaries. Our study shows that hormone substitution may have an impact on uterus growth and that therefore vaginosonographical monitoring can be recommended.     

Characteristics of surfactant formation in response to injection of exogenous particles into the lungs

Laboratory of Pathogenesis and Experimental Therapy of Pneumoconioses, N. I. Pirogov Second Moscow Medical Institute. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 109, No. 2, pp. 128–130, February, 1990.     

Declining socioeconomic differences in the use of menopausal and postmenopausal hormone therapy in Finland

Objective: Sales figures for the use of menopausal and postmenopausal hormone therapy in Finland show a rapid increase during the 1980s continued into the first half of the 1990s. Hormone therapy use became very common in Finland compared to many other Western countries. The aim of our study was to investigate the sociodemographic distribution of hormone therapy among Finnish women aged 45–64 years. Methods: The study is based on population-based surveys conducted in 1989 and 1996 (response rates 87% and 78%). Results: Between 1989 and 1996 the current use of hormone therapy increased from 22% to 27%; in 1989 it was most common in the age group 50–54 years, but in 1996 among 55–59-year-olds. In 1989 it was significantly more common among women with longer education than other women in every age group, but in 1996 this difference was significant only in those 55 years and older. In 1989 the use was more common in the capital area than elsewhere and this difference decreased but remained significant in 1996. Conclusion: Our results suggest that hormone therapy has become a routine treatment during the menopause in all educational groups and throughout the country. The lack of socioeconomic differences indicates that among women under 55 year of age the saturation point in short-term hormone use was reached in 1996. However, the persistence of socioeconomic differences among older women suggests that the use of long-term postmenopausal hormone therapy will continue to increase for some time.     

Untreated growth hormone deficiency with extremely short stature, bone dysplasia, cleft lip--palate and severe mental retardation in a 26-year-old man with a de novo unbalanced translocation t(1;12)(q24;q24)

We report on a 26-year-old patient presenting with extremely short stature (height 72 cm, weight 6.5 kg, OFC 42.5 cm), facial dysmorphism, cleft lip–palate, severe mental retardation and de novo 1q24.2–q25.2 and 12q24.31 interstitial deletion. He was the only child of non-consanguineous parents and his birth length was 43 cm. He had severe feeding difficulties and required enteral nutrition until the age of 3 years. Standard cytogenetic analysis showed an apparently balanced de novo translocation t(1;12)(q24;q24). Endocrine studies at 11 years of age for severe growth retardation revealed multiple pituitary hormone deficiency with severe growth hormone deficiency, but the child was untreated because of associated mental retardation. At 26 years of age, he could not walk or speak and had no signs of puberty. Investigations revealed spondylo-epi-metaphyseal dysplasia with severe osteoporosis, enlarged aorta when compared to the patient's size and apparently normal pituitary development. High resolution karyotype showed a 1q24–q25 deletion, and comparative genomic hybridization studies confirmed the 1q interstitial deletion. FISH studies of both breakpoints using PACs and BACs enabled us to further characterize the 1q interstitial deletion (1q24.2–1q25.2) and also revealed a 12q24.31 interstitial microdeletion. This case is compared with previously reported patients with similar deletions, but the untreated pituitary deficiency could also be responsible in part for the severity of the growth deficiency. This observation is of interest for two reasons. First, these deletions could be a clue in the search for a gene responsible for growth hormone deficiency/midline defects. Second, it shows the importance of molecular cytogenetics in the study of de novo apparently balanced translocation with abnormal phenotype.     

Elevation of dental pain threshold induced in man by physical exercise is not reversed by cyproheptadine-mediated suppression of growth hormone release

The effect of cyproheptadine on growth hormone (GH) secretion and dental pain threshold elevation during physical exercise was studied in healthy human subjects. Different levels of exercise (200–300 W) were produced by a cycle-ergometer. Dental pain thresholds were tested with a constant current pulp tester. In all 6 subjects dental pain thresholds and the heart rate were increased with increasing work load. Cyproheptadine did not have any significant effect on dental pain threshold elevations, although it suppressed the exercise-induced GH release. The results indicate that the exercise-induced dental pain threshold elevation is not based on GH-related stress mechanisms, since cyproheptadine did not reverse the pain threshold elevation.     

Monoclonal antibodies reactive with myelin basic protein

New monoclonal antibodies (MAbs) to myelin basic protein (BP) reveal epitopes to be in sequences 22–34, 75–82, 83–96, 118–131 and 125–131. Comparison of these results with those previously reported suggest that almost every sequence of about 10 amino acid residues may be sufficiently antigenic to make a single MAb but that certain regions are immunodominant, strong enough to make practically the same MAb repeatedly. One of these new MAbs (clone 3) has especially interesting reactivity, sharply limited to residues 75–82 in bovine and porcine BP: Lys-Ala-Gln-His-Gly-Arg-Pro. Whales presumably have the same sequence, since their BPs are fully reactive with clone 3 MAb, but all other species of BP, with known sequences of BP, have at least two changes in this sequence. Deletion of Lys⁷⁵ (as in a tryptic peptide of porcine BP) reduces reactivity with the MAb about 10-fold, whereas substitution of Ala⁷⁶ by Ser (as in all other species of BP) and either deletion of Gln⁷⁷ (as in human, monkey and rabbit BP) or His⁷⁸ (as in the guinea pig and rat BP) or substitution of Pro⁸² by Thr (as in human, monkey, rat and mouse BP) eliminates reactivity. We speculate that woodchuck and prairie dog BPs in this region closely resemble chicken BP, which has about 2% of the original reactivity. However, squirrel BP is unique, probably having only one of the changes in this region of BP, since it possesses 10–20 times the reactivity of chicken BP but still only 20–50% of the original reactivity with clone 3 MAb, a degree of reactivity not seen with any other species of BP.     

Pituitary hormonal profile in menopause

The hormonal profile of pituitary hormones was studied by measuring serum FSH, LH, TSH, prolactin (PRL) and growth hormone (GH) in a series of postmenopausal women 50–85 yr old who were at least 1 yr postmenopausal.

In 116 women mean (±SD) plasma FSH and LH were 55.8 ± 22 mU/ml and 25.6 ± 13.62. In 27 women, 1–5 yr after the menopause (M), mean FSH was 56 ± 23.8 and LH 24.7 ± 11 mU/ml and in 22 women, 6–9 yr after M, FSH was 60.3 ± 24.6 mU/ml and LH 27.9 ± 17.2 mU/ml. There was then a gradual, but not statistically significant (n.s.) fall of FSH and LH to 51.6 ± 22.6 and 23.9 ± 9 in 23 women, 20 or more years after M.

TSH was measured in 75 women and its mean value was 4.3 ± 2.4 μU/ml. Three hypothyroid values (70, 20 and 13.5 μU/ml) were also found. Mean TSH value in 20 women aged 50–54 yr (4 ± 2.7 μU/ml) was not significant compared to other age-groups or to 8 women aged 70–85 yr (4.57 ± 2.5 μU/ml).

Mean PRL in 62 cases was 0.54 ± 0.20 mU/ml. In 17 other women unexplained increased values (>1 mU/ml) of PRL were found. No significant change of PRL was found with advancing age.

Mean GH in 32 women was 3.7 ± 2.6 ng/ml. Eight other values were found <1 ng/ml and 3 above 10 ng/ml. The distribution of values in the age-group 50–59 yr (n = 22) did not differ from the age-group 60–85 yr (n = 21).

It is concluded that the basal concentration of gonadotrophins, after an initial rise, as well as that of the other pituitary hormones remains practically unaltered with advancing age in postmenopausal women.     

Radioautographic identification of lactogen binding sites in rat median eminence using 125I-human growth hormone: Evidence for a prolactin “short-loop” feedback site

Summary The binding characteristics of human growth hormone were exploited to identify radioautographically lactogen binding sites in the rat median eminence. Following systemic injection ¹²⁵I-human growth hormone bound preferentially to the lateral palisade zone, a region of median eminence rich in dopamine and LHRH. Coinjection of ¹²⁵I-human growth hormone with an excess of unlabeled human growth hormone or ovine prolactin, but not bovine growth hormone, competitively blocked ¹²⁵I-human growth hormone binding to the external median eminence. These observations provide direct evidence of recognition sites for lactogenic hormones in a discrete region of the median eminence associated with hypothalamic regulation of hypophyseal prolactin and luteinizing hormone secretion. Median eminence lactogen binding sites may mediate presumed direct effects of lactogenic hormones on the reproductive functions of the hypophysiotropic hypothalamus.A preliminary report of these findings was presented at the Annual Meeting of the Canadian Society for Clinical Investigation, February 5, 1979, Montreal, and appeared in Clinical Research 26, 874A (1979)     

Hypothalamus of the human fetus

The organization of the human hypothalamus was studied in 31 brains aged from 9 weeks of gestation (w.g.) to newborn, using immunohistochemistry for parvalbumin, calbindin, calretinin, neuropeptideY, neurophysin, growth associated protein GAP43, synaptophysin and glycoconjugate, 3-fucosyl-N-acetyl-lactosamine. Morphogenetic periods 9–10 and 11–14 w.g. are characterized by differentiating structures of the lateral hypothalamic zone, which give rise to the lateral hypothalamus (LH) and posterior hypothalamus. The perifornical nucleus differentiates at 18 w.g., from LH neurons which remain anchored in the perifornical position while most of the LH cells are displaced laterally. A transient supramamillary nucleus was apparent at 14 w.g. but not after 16 w.g. As the ventromedial nucleus differentiated at 13–16 w.g., three principal parts; the ventrolateral, the dorsomedial and the shell were revealed by distribution of calbindin, calretinin and GAP43 immunoreactivity. Morphogenetic periods 15–17, 18–23 and 24–33 w.g. are characterized by differentiation of the hypothalamic core, in which calbindin positive neurons revealed the medial preoptic nucleus at 16 w.g. abutted laterally by the intermediate nucleus. The dorsomedial nucleus was clearly defined at 10 w.g. and consisted of compact and diffuse parts, an organization that was lost after 15 w.g. Differentiation of the medial mamillary body into lateral and medial was seen at 13–16 w.g. Morphogenetic period after 34 w.g. was marked by differentiation of midline zone structures including suprachiasmatic, arcuate and paraventricular nuclei. The findings of the present study provide for a better understanding of the structural organization of the adult human hypothalamus, produce new evidence for homologies with the better studied rat hypothalamus and underpin staging system for fetal human hypothalamic development.     

Effects of atrial natriuretic factor on anterior pituitary hormone secretion in normal man

Summary The effects of intravenous human atrial natriuretic factor ANF(99-126) administration on anterior pituitary hormone secretion have not been extensively investigated in humans. We repeatedly studied 10 healthy volunteers (5 female, 5 male, aged 28±2 years) on 2 occasions, 3 days apart. In randomized, single blind order, subjects received pretreatment with either placebo or intravenous ANF(99–126) (bolus 100 g/kg, 30-min infusion of 0.1 g/kg-min). Subsequently, on both occasions subjects received a combined intravenous bolus injection of pituitary releasing hormones (200 pg thyrotropin releasing hormone, 100 g gonadotropin releasing hormone, 50 g growth hormone releasing hormone and 100 g human adrenocorticotropin releasing hormone; Bissendorf, Hannover, FRG). Plasma concentrations of adrenocorticotropic hormone (ACTH), cortisol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), growth hormone (GH), thyrotropin (TSH), prolactin, ANF and cyclic guanosine monophosphate (GMP) were determined by radioimmunoassay. ANF(99–126) treatment induced a significant reduction in basal ACTH plasma concentrations and tended to decrease basal plasma cortisol. The TSH response to combined releasing hormone administration was significantly diminished after ANF(99-126) pretreatment. In women, the releasing hormone induced prolactin increase was reduced after ANF(99–126) pretreatment. With the present study design, ANF(99–126) did not alter the basal or releasing hormone stimulated plasma concentrations of cortisol, LH, FSH and GH. Releasing hormone administration did not affect ANF and cyclic GMP plasma levels. In humans, effects of natriuretic peptides on anterior pituitary hormone secretion may have to be considered with investigational or therapeutic administration of ANF analogues or agents interfering with the ANF metabolism.Abbreviations ANF(99–126) human atrial natriuretic factor - ACTH adrenocorticotropic hormone - LH luteinizing hormone - FSH follicle-stimulating hormone - GH growth hormone - TSH thyrotropin - PRL prolactin - cyclic GMP cyclic guanosine monophosphate - TRH thyrotropin releasing hormone - GnRH gonadotropin releasing hormone - GHRH growth hormone releasing hormone - CRH adrenocorticotropin releasing hormone     

Antibodies against different epitopes of heat-shock protein 60 in children with type 1 diabetes mellitus

The aim of this study was to investigate the amounts and epitope specificity of antibodies against heat shock protein 60 (hsp60) in the sera of type 1 diabetic and healthy children. Antibodies specific for peptide p277 of human hsp60 and of M. bovis as well as for human hsp60, M. bovis hsp65 proteins were measured by ELISA. Other autoantibodies (islet cell antibodies, glutamate decarboxylase antibodies and IA-2 antibodies) were also determined. A total number of 83 serum samples from children with type 1 diabetes mellitus and 81 samples of control children were investigated. Epitope scanning of the hsp60 for linear antibody epitopes was carried out using synthetic peptides attached to pins. The antibody levels specific for peptide p277 of human- and of M. bovis origin were significantly (human: P=0.0002, M. bovis: P=0.0044) higher in the diabetic children group than in the healthy children. We could not find significant difference in the antibody levels to whole, recombinant hsp proteins among the examined groups of children. Antibodies to two epitope regions on hsp60 (AA394–413 and AA435–454) were detected in high titres in sera of children with diabetes mellitus. The first region similar to the sequence found in glutamate decarboxylase, whereas the second one overlaps with p277 epitope to a large extent. Presence of antibodies to certain epitopes of hsp60 (AA394–413—glutamic acid decarboxylase-like epitope; AA435–454—p277-like epitope) in diabetic children may reflect their possible role in the autoimmune diabetogenic process of the early diabetes.     

Effect of frequency of growth hormone administration on longitudinal bone growth and body weight in hypophysectomized rats

JANSSON, J.-O., ALBERTSSON-WIKLAND, K., EDÉN, S., THORNGREN, K.-G. and ISAKSSON, O.: Effect of frequency of growth hormone administration on longitudinal bone growth and body weight in hypophysectomized rats. Acta Physiol Scand 1982, 114 :261–265. Received 11 May 1981. ISSN 0001–6772. Department of Physiology, University of Göteborg and Department of Orthopaedic Surgery, University of Lund, Sweden. The effect of frequency of growth hormone (GH) administration on longitudinal bone growth and body weight was studied in hypophysectomized rats. Replacement therapy with 3 different doses of human GH [(hGH) Crescormone®] was started 10–14 days after hypophysectomy and was continued for 5 days. Longitudinal bone growth, as measured by the tetracycline method, and body weight were determined during the injection period. With a daily replacement dose of 128 μg of hGH body weight gain and longitudinal bone growth were significantly higher when the hormone was injected 4 and 8 times per day compared with animals receiving the hormone in one daily injection. When the dose of hGH was 32 or 8 μg per day, longitudinal bone growth and body weight gain were more pronounced in animals receiving the hormone 2 and 4 times per day compared with animals receiving the hormone one or 8 times per day. The results of the present study demonstrate that the frequency of GH administration influence body growth. The findings suggest that the secretory pattern of GH influence the growth rate under in vivo condition.     

Morphometric study of the brachiobicarotid trunk in human fetuses

The study was conducted to define a normal range for the length, external diameter and volume of the brachiobicarotid trunk during gestation. The material examined consisted of 128 human fetuses of both sexes (63 male, 65 female) aged from 15 to 34 weeks, from spontaneous abortions or stillbirths. The arterial bed was filled with white latex LBS 3060, specimens were fixed in a 10% formalin, and then branches of the aortic arch were dissected, recorded using a camera, and digitalized to JPEG images. Afterwards, the brachiobicarotid trunks underwent morphometric analysis with the digital image analysis system of Leica QWin Pro16. Regression analysis was used to investigate the growth of the brachiobicarotid trunk during gestation. The brachiobicarotid trunk was observed in 27 of the 128 fetuses studied (21.09%). The results showed the brachiobicarotid trunk length as a function of fetal age, which could be expressed by y=−1.250+0.1433x±0.7682, and the brachiobicarotid trunk diameter by y=−3.034+0.2845±0.4253. The volumetric growth of the brachiobicarotid trunk followed the quadratic function y=178.5−19.69x+0.545x²±20.112. The correlation coefficients between arterial length or external diameter and fetal age, and the coefficient of determination between arterial volume and fetal age were as follows: r=0.76 for length, r=0.97 for external diameter, and R²=0.84 for volume (P<0.001). The relative diameter of the brachiobicarotid trunk increased from 0.738±0.089 to 0.916±0.088 during the study period.     

Changes in somatotropin and thyrotropin secretory patterns in aging rats

In order to clarify whether pituitary enlargement influences the secretory patterns of growth hormone (GH) and thyrotropin (TSH) in old rats, we studied the correlation between pituitary weight and plasma levels of GH and TSH in Sprague-Dawley rats of different age and sex. Young female (3–4 months; YF), old female (25 months; OF), and senescent female (33–35 months; SF) rats and young male (3–4 months; YM) and old male (24–26 months; OM) rats carrying chronic intraatrial cannulas were used. Sequential blood samples were removed through the cannulas while the animals remained conscious and undisturbed. Plasma TSH and GH as well as serum thyroxine (T₄) and triiodothyronine (T₃) were measured by radioimmunoassay. At two years of age, both males and females showed a consistent decline in GH pulse amplitude without change in trough levels. By 33–35 months of age, females showed a reversal in the previous pattern of change for GH secretion: pulse amplitude, trough levels, and mean plasma GH increased significantly with respect to the old females. The correlation between mean plasma GH and anterior pituitary (AP) weight was positive and significant (p<0.01) for females but nonsignificant for males. Old and senescent rats showed significantly lower serum T₄, but not T₃, than young animals while plasma TSH increased with age in both sexes. The present results show for the first time that senescent females hypersecrete GH and suggest that the age-related alteration of TSH secretion in rats may be due to the low levels of T₄ present in the aged animals. The correlation analysis shows that pituitary enlargement is in general associated with increased secretion of both GH and TSH in senescent female rats.